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Objective:To characterize the longitudinal and dynamic high-density lipoprotein (HDL) trajectories in critically ill children and explore their correlation with clinical outcomes.Methods:Retrospective cohort study.All critically ill children admitted to the Pediatric Intensive Care Unit (PICU) of West China Hospital, Sichuan University from January 1, 2015 to October 1, 2020 were included in this retrospective study.Group-based trajectory modeling (GBTM) was applied to characterize the HDL trajectories in days 0-6 post-PICU admission and develop HDL trajectory groups.The in-hospital mortality rate was reported as frequency (%) and then compared by the Chi-square test or Fisher′s exact test between HDL trajectory groups.The length of stay (LOS) in the PICU was described by M( Q1, Q3), and its difference between HDL trajectory groups was evaluated by the Kruskal Wallis test.Logistic regression and multiple linear regression were used to determine the correlation between HDL trajectories and clinical outcomes.The primary outcome was in-hospital mortality rate, and the secondary outcome was LOS in the PICU. Results:A total of 4 384 critically ill children were ultimately enrolled in the study, and 6 HDL trajectory groups were developed based on GBTM analyses: group 1 (758 cases), the lowest HDL group; group 2 (1 413 cases), the low HDL group; group 3 (74 cases), the low-to-high HDL group; group 4 (621 cases), the medium HDL group; group 5 (1 371 cases), the high HDL group; and group 6 (147 cases), the highest HDL group.Logistic regression analysis showed that compared with critically ill children in group 1, those belonging to groups 2, 3, 4, 5, and 6 were at lower risks of in-hospital mortality with odds ratio ( OR): 0.475, 95%confidence interval ( CI): 0.352-0.641, P<0.001; OR: 0.093, 95% CI: 0.013-0.679, P=0.019; OR: 0.322, 95% CI: 0.208-0.479, P<0.001; OR: 0.263, 95% CI: 0.185-0.374, P<0.001, and OR: 0.142, 95% CI: 0.044-0.454, P=0.001, respectively.Multiple linear regression analysis revealed that compared with critically ill children in group 1, those belonging to groups 4, 5, and 6 had the trend of shorter LOS in PICU, and the β value and 95% CI were β: -4.332, 95% CI: -5.238- -3.426, P<0.001; β: -3.053, 95% CI: -3.809--2.297, P<0.001; β: -6.281, 95% CI: -7.842--4.721, P<0.001, respectively. Conclusions:The dynamic HDL trajectories during 0-6 days after PICU admission are associated with in-hospital mortality rate of critically ill children.The HDL trajectory at a persistently low level is associated with higher mortality, while the HDL trajectory at a persistently high level or with the trend from a low level rising to a high level shows a lower risk of mortality.It is suggested that the HDL trajectory model may become an indicator to predict the condition and prognosis of critically ill children.
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Objective To investigate the diagnostic value of cervical vagus nerve cross-sectional area(CAS)for Parkinson's disease(PD).Methods Thirty patients with PD admitted to the People's Hospital of Zhengzhou University from October 2019 to October 2022 were selected as PD group,25 patients with multiple system atrophy(MSA)admitted to the People's Hospital of Zhengzhou University during the same period were selected as the MSA group,and 30 healthy individuals who underwent physical examination in the People's Hospital of Zhengzhou University during the same period were selected as healthy control group.Cervical vagus CAS of subjects in the three groups were measured by high-resolution ultrasound,and the difference of CAS of cervical vagus nerve was compared among the three groups.The degree of impairment of autonomic nervous function of subjects in the three groups was evaluated by PD autonomic symptom scale(SCOPA-AUT).The diagnostic value of cervical vagus nerve CAS for PD was analyzed by receiver operating characteristic(ROC)curve.Results The CAS of the right cervical vagus nerve of subjects was significantly larger than that of the left in the healthy control group and PD group(P＜0.05);there was no significant difference in CAS of bilateral cervical vagus nerve of subjects in the MSA group(P＞0.05).The CAS and average CAS of bilateral cervical vagus nerve of subjects in the PD group and MSA group were significantly lower than those in the healthy control group(P＜0.01).The CAS of the right vagus nerve of subjects in the MSA group was significantly lower than that in the PD group(P＜0.05);there was no significant difference in CAS and the average CAS of the left vagus nerve between the MSA group and the PD group(P＞0.05).The total score of SCOPA-AUT and gastrointestinal(GI),cardiovascular(CV),urinary(UR)and sexual(SX)scores of subjects in the PD group and MSA group were significantly higher than those in the healthy control group(P＜0.01).The total score of SCOPA-AUT and UR,SX scores of subjects in the MSA group were significantly higher than those in the PD group(P＜0.05).There was no significant difference in temperature(TH)and pupil(PU)of subjects among the three groups(P＞0.05).Pearson correlation analysis showed that the CAS of cervical vagus nerve of PD patients was not correlated with the total score of SCOPA-AUT and the UR,TH,PU,SX scores(r=-0.143,0.281,0.297,0.265,0.312;P＞0.05).The CAS of cervical vagus nerve of PD patients was negatively correlated with GI and CV scores(r=-0.683,-0.373;P＜0.05).ROC curve analysis showed that the area under the curve of cervical vagus nerve for diagnosing PD was 0.870(95％confidence interval:0.773-0.966,P＜0.05);the critical value was 3.064 mm2,the sensitivity was 96％,and the specificity was 67％.The area under the curve of CAS of cervical vagus nerve in differential diagnosis of PD,MSA was 0.680(95％confidence interval:0.537-0.823,P＜0.05).The sensitivity and specificity for the diagnosis of MSA were 68％and 70％when the CAS of the cervical vagus nerve＜2.709 mm2.Conclusion The CAS of cervical vagal nerve has high clinical diagnostic value for PD,and it provides a new way to improve the diagnosis rate of PD.
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Objective:To compare the clinical efficacy of femoral distraction and homeopathic double reverse traction reduction assisted internal fixation in the treatment of Schatzker type IV-VI tibial plateau fractures.Methods:A total of 51 patients (28 males and 23 females) with Schatzker IV-VI tibial plateau fractures treated with femoral distraction or homeopathic double reverse traction reduction from January 2017 to June 2021 in the Second Affiliated Hospital of Wenzhou Medical University were retrospectively analyzed. The average age was 49.6±11.9 years (range, 28-71 years). The time from injury to operation was 4.5±3.0 days (range, 1-15 days). There were 5 cases with combined anterior cruciate ligament injuries and 9 cases with posterior cruciate ligament injuries. Twenty-five cases were treated with femoral distraction reduction (distraction reduction group) and 26 cases with homeopathic double reverse traction reduction (traction reduction group). The operation time, intraoperative blood loss, visual analogue scale (VAS) on the first day after operation, hospitalization time, fracture healing time, and incidence of complications were compared between the two groups. Hospital for Special Surgery (HSS) knee function score at 1, 3, 6, 12 months after operation were also compared.Results:All patients were operated successfully. The operation time was 125.9±35.1 min (range, 60-220 min), and the intraoperative blood loss was 138.4±85.4 ml (range, 30-400 ml). 15 patients received autologous iliac bone grafting and 36 patients received allogeneic bone grafting. The VAS score on the first day after operation was 2.4±0.7 (range, 1-4), the hospital stay was 12.6±3.6 days (range, 7-24 days), and the fracture healing time was 14.6±2.2 weeks (range, 12-21 weeks). All patients were followed up for 16.8±2.8 months (range, 13-25 months). The operation time, intraoperative blood loss and hospital stay in the traction reduction group were 106.2±21.7 min, 86.9±42.6 ml and 11.6±3.3 days, respectively, which were less than 146.4±34.9 min, 192.0±86.2 ml and 13.7±3.6 days in the distraction reduction group. The differences were statistically significant ( P<0.05). The HSS scores of traction reduction group at 1 month and 3 months after operation were 83.8±1.7 and 86.7±2.0, which were higher than those of distraction reduction group (81.0±2.6 and 84.9±2.6), and the differences were statistically significant ( P<0.05). There was no significant difference in HSS score between the two groups at 6 and 12 months after operation ( P>0.05). Conclusion:The internal fixation treatment of Schatzker type IV-VI tibial plateau fracture assisted with homeopathic double reverse traction reduction can reduce the amount of intraoperative blood loss, operation time and hospital stay, and improve the knee function in the early postoperative period.
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Long non-coding RNAs (lncRNAs) can affect various biological processes, such as cell proliferation, migration, and angiogenesis, by regulating chromosome remodeling, gene transcription or protein translation. This review summarizes recent research progress in the role of lncRNAs in the occurrence and development of infantile hemangioma, in order to provide new directions for the treatment of infantile hemangioma.
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Objective:To investigate the role of plasma neurofilament light chain (NfL) in diagnosing and differentiating Parkinson's disease (PD) and multiple system atrophy-Parkinsonian subtype (MSA-P).Methods:Forty PD patients and 23 MSA-P patients admitted to Department of Neurology, Henan Provincial People's Hospital from June 2019 to December 2021 were recruited; 27 healthy subjects accepted physical examination during the same period were selected as controls. Ultrasensitive Simoa technology was used to measure the plasma NfL. Differences in clinical data and plasma NfL were compared among all subjects. Correlations of plasma NfL with clinical characteristics, such as disease course, Hoehn-Year (H-Y) staging, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT) and levodopa equivalent daily dosage (LEDD), were analyzed with Pearson correlations. Receiver operating characteristic (ROC) curve was used to analyze the value of plasma NfL in diagnosing and differentiating PD and MSA-P.Results:Compared with MSA-P group, PD group had significantly longer disease course and statistically lower scores of UPDRS-II and SCOPA-AUT ( P<0.05). The plasma NfL in MSA-P group, PD group and healthy control group was decreased successively ([37.69±10.47] pg/mL, [17.85±4.23] pg/mL, [12.86±3.14] pg/mL, respectively), with statistical differences ( P<0.05). In MSA-P patients, Pearson correlations showed positive correlation between plasma NfL and age ( r=0.442, P=0.035); and Partial correlations showed positive correlations between plasma NfL and scores of UPDRS-I and UPDRS-III ( P<0.05), and plasma NfL showed no significant correlation with H-Y staging, UPDRS-III, MoCA, LEDD or SCOPA-AUT scores ( P>0.05). In PD patients, Pearson correlations showed that plasma NfL was positively correlated with age ( r=0.342, P=0.031); partial correlations showed that plasma NfL was positively correlated with H-Y staging and UPDRS-III, and negatively correlated with MoCA scores ( P<0.05); plasma NfL showed no significant correlation with disease course, scores of UPDRS-I and UPDRS-II, LEDD, and SCOPA-AUT scores ( P>0.05). ROC curve showed that the area under the curve (AUC) of plasma NfL in diagnosing PD was 0.814 (95% CI: 0.712-0.920, P<0.001); AUC of plasma NfL in differentiating and diagnosing PD and MSA-P was 0.980 (95% CI: 0.954-1.000, P<0.001); AUC of plasma NfL in diagnosing MSA-P was 0.998 (95% CI: 0.993-1.000, P<0.001). Conclusions:Plasma NfL is correlated with severity of motor symptoms in MSA-P patients; plasma NfL is correlated with cognitive function and disease course in PD patients. Besides, plasma NfL has high sensitivity and specificity in differentiating PD and MSA-P, therefore, plasma NfL could serve as a biomarker to diagnosis and differentiate PD.
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Objective:To observe any therapeutic effect of combining botulinum toxin type A (BTX-A) with rehabilitation training in treating Parkinson′s disease (PD) patients with striatal foot deformity (SFD).Methods:A total of 68 PD patients with SFD were randomly divided into a control group and a treatment group. Both groups were given routine medication with pramipexole and dopamine receptor agonists and received lower limb rehabilitation training, including passive activity training, strength training and walking training. The treatment group was additionally injected with BTX-A. Sciatic pain was quantified using a visual analogue scale. The Unified Parkinson′s Disease Rating Scale-lower limb motor lower limb motor function (UPDRS-LLM) scale, the Berg balance scale and the modified Barthel index were applied to test all of the participants before the experiment and on the 7th, 14th and 30th day of the treatment.Results:The average scores of the control group on all of measures at were significantly better than those of the control group at the same time points, and by the 14th and 30th day had improved significantly compared with those before treatment.Conclusion:Supplementing rehabilitation training with BTX-A can significantly improve foot deformity and relieve the muscle tension and spastic pain of PD patients with SFD, promoting the motor functioning of their lower limbs, their balance and their performance in the activities of daily living.
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Objective:To compare the effects of milnacipran and paroxetine on anxiety state and headache severity of patients with generalized anxiety disorder (GAD).Methods:Ninety-six patients with GAD treated in Zaozhuang Mental Health Center from January 2019 to September 2020 were selected and randomly divided into the paroxetine group (treatment with oral paroxetine) and the milnacipran group (treatment with oral milnacipran), each group with 48 cases. A course of treatment consists of 4 weeks. After 3 months of regular medication, the clinical efficacy, Hamilton Anxiety Scale (HAMA) scores, visual analogue scale (VAS) scores, migraine-specific quality of life questionnaire (MSQ V2.1) scores, and Headache Impact Test-6 (HIT-6) scores were compared between the two groups. Adverse reactions during the treatment were recorded in both groups.Results:The total effective rate in the milnacipran group at 4 weeks and 3 months after treatment were significantly higher than those in the paroxetine group: 47.92%(23/48) vs. 22.92%(11/48), χ2 = 6.56, P<0.05; 75.00%(36/48) vs. 51.47%(26/48), χ2 = 4.55, P<0.05. After treatment for 4 weeks and 3 months, the HAMA scores, VAS scores, MSQ V2.1 scores and HIT-6 scores in the milnacipran group were significantly lower than those in the paroxetine group ( P<0.05). The difference of incidence of adverse reactions in the two groups had no statistical significance ( P>0.05). Conclusions:For patients with GAD, the treatment effect of milnacipran is more significant than paroxetine, which can not only reduce patients′ anxiety state and headache degree, but also improve their specific quality of life, with high safety.
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Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.
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Objective:To analyze demographic and clinical characteristics of infantile hemangioma (IH) , and to explore related risk factors for IH.Methods:A multicenter case-control study was conducted. IH patients (case group) and healthy children (control group) were collected from West China Hospital of Sichuan University, West China Second University Hospital of Sichuan University and Yulin Community Central Hospital of Chengdu from October 2018 to December 2020. The data on patients′ demographic characteristics, and risk factors during their mothers′ pre-pregnancy, pregnancy and perinatal period were collected and retrospectively analyzed. Univariate and multivariate analyses were performed using binary logistic regression.Results:A total of 1 479 patients with IH and 1 086 healthy children were included in this study. There were 456 males and 1 023 females in the case group, with the age being 3.74 ± 2.82 months, and there were 359 males and 727 females in the control group, with the age being 3.95 ± 2.77 months. There was no significant difference in the gender ratio, age, ethnic composition, birth weight or birth height between the case group and control group (all P > 0.05) . IH lesions mostly affected the head and face (564 cases, 38.1%) , followed by the trunk (449 cases, 30.6%) and limbs (356 cases, 24.1%) . At the visit, 1 109 (75.0%) patients presented with proliferating IH, 1 059 (71.6%) with superficial IH, and 1 306 (88.3%) with focal IH. The IH lesion area ranged from 0.01 to 168.00 (6.24 ± 12.91) cm 2, and the segmental IH area ranged from 7.50 to 168.00 (32.17 ± 26.94) cm 2. Univariate logistic regression analysis showed some factors influencing the occurrence of IH (all P < 0.05) , including pre-pregnancy factors (delivery history and miscarriage history) , pregnancy factors (fetal distress, cord entanglement, history of threatened abortion, placenta previa, oligohydramnios, gestational hypothyroidism, gestational anemia, history of progesterone supplementation, history of thyroxine drug use, history of uterus myomas) , and perinatal factors (including fetal position, gestational weeks, premature rupture of membranes and preterm premature rupture of membranes) . Multivariate binary logistic regression adjusted analysis showed that fetal breech presentation, preterm birth, cord entanglement and history of thyroxine drug use during pregnancy did not influence the occurrence of IH (all P > 0.05) ; the delivery history was the strongest independent risk factor for IH (adjusted OR = 5.624, 95% CI: 4.275 to 7.398, P < 0.001) , and gestational hypothyroidism and history of uterus myomas were protective factors for IH. Conclusions:In this study, the average age of IH patients at visit was 4 months, skin lesions mostly occurred on the head and face, and most were superficial and focal in the proliferative stage. The occurrence and development of IH may be associated with placental diseases, hypoxia, maternal hormone levels during pregnancy, etc.
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Objective:To investigate the effect of the glucose transporter 1 (Glut-1) inhibitor resveratrol on the activity of infantile hemangioma (IH) -derived endothelial cells (HemEC) .Methods:IH tissues were collected from 4 cases of proliferating IH and 4 cases of involuting IH, and immunohistochemical study was performed to determine the Glut-1 expression. Primary HemEC were extracted from 4 proliferating IH tissues, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of Glut-1 in HemEC and human umbilical vein endothelial cells (HUVEC) , respectively. HemEC were cultured in vitro and treated with 0 (control group) , 50, 100, 200, 400 and 800 μmol/L resveratrol for 24 hours, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HemEC in the above groups, and the 50% inhibitory concentration (IC50) was calculated. The migratory ability and apoptosis level of HemEC were assessed by Transwell assay and flow cytometry, respectively. Intergroup comparisons were performed using t test or analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Immunohistochemical study showed that Glut-1 was expressed in vascular endothelial cells derived from both proliferating and involuting IH tissues, and the Glut-1 expression was abundant in the proliferating IH but markedly decreased in the involuting IH tissues. The mRNA and protein expression levels of Glut-1 were significantly higher in HemEC (1.793 ± 0.041, 1.959 ± 0.144, respectively) than in HUVEC (0.820 ± 0.073, 0.648 ± 0.046, t = 16.35, 12.28, respectively, both P < 0.001) . After the treatment with Glut-1 inhibitor resveratrol at different concentrations, the proliferative ability of HemEC significantly differed among the control group, 50-, 100-, 200-, 400- and 800-μmol/L resveratrol groups ( F = 1 043.00, P < 0.001) , and was significantly lower in all the resveratrol groups than in the control group (all P < 0.05) . The IC50 of resveratrol was calculated to be 150 μmol/L by using GraphPad Prism 8 software. Transwell assay and flow cytometry showed significantly decreased number of migratory HemEC but significantly increased apoptosis rate respectively in the 150 μmol/L resveratrol group (61 ± 5, 13.01% ± 0.45%, respectively) compared with the control group (150 ± 6, 3.93% ± 0.68%, t = 15.11, 19.34, respectively, both P < 0.001) . Conclusion:The key glycolytic enzyme Glut-1 was highly expressed in proliferating IH tissues and HemEC, and resveratrol could inhibit the proliferation and migration of HemEC, but promote their apoptosis.
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Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.
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Objective:To investigate the correlation between total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio and unstable carotid plaque.Methods:From February 2021 to May 2021, adult patients with asymptomatic carotid atherosclerotic plaque admitted to the Department of Neurology, the First People's Hospital of Lianyungang were retrospectively enrolled. The demographic and related clinical data were collected. Carotid artery plaques were detected by ultrasound, and the subjects were divided into a stable plaque group and an unstable plaque group. Multivariate logistic regression analysis was used to assess the independent risk factors for unstable carotid plaques. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of TC/HDL-C ratio for unstable carotid plaques. Results:A total of 362 patients with asymptomatic carotid atherosclerotic plaque were enrolled, including 226 (62.43%) in the stable plaque group and 136 (37.57%) in the unstable plaque group. Multivariate logistic regression analysis showed that after adjusting for confounding factors, only TC/HDL-C ratio was the independent risk factor for unstable carotid plaque (taking the 1 st quintile array of TC/HDL-C ratio as a reference, the 4 th quintile array: odds ratio 3.13, 95% confidence interval 1.50-6.55, P=0.002; the 5 th quintile array: odds ratio 6.75, 95% confidence interval 3.21-14.22, P<0.001). ROC curve analysis showed that the area under the curve of TC/HDL-C ratio for predicting unstable carotid plaque was 0.691 (95% confidence interval 0.634-0.748; P<0.001), the optimal cut-off value was 4.38, and the sensitivity and specificity were 50.0% and 82.7%, respectively. Conclusion:TC/HDL-C ratio is an independent risk factor for unstable carotid plaques and has a certain predictive value for unstable carotid plaques.
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A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses
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Lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.
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Objective:To investigate the effect of Donepezil treatment on the expression of high mobility group box 1 protein(HMGB1)in serum and cerebrospinal fluid in Alzheimer's disease patients.Methods:This is a single-center observational stady.A total of 120 Alzheimer's disease patients admitted in our hospital from March 2017 to may 2019 were randomly divided into the control group receiving the routine drug therapy(n=60)and the Donepezil group receiving Donepezil hydrochloride(5 mg/d)as an add-on to medicine of control group(n=60). The expression levels of HMGB1 in serum and cerebrospinal fluid, Alzheimer's disease assessment scale(ADAS-Cog), mini-mental state examination(MMSE)scores, activities of daily living(ADL)and neuropsychiatric inventory(NPI)were compared before versus after 1 month of treatment.Results:After the Donepezil treatment, the ADAS-Cog score was lower, MMSE score was higher, ADL score was higher and NPI score was lower in the Donepezil group than in the control group(25.2± 2.7 vs.33.4± 3.6, 23.3± 2.1 vs.19.4±1.9, 56.3±2.1 vs.46.9±1.6, 16.2±2.3 vs.22.3± 2.6, P<0.05). After the Donepezil treatment, the levels of HMGB1 in serum[(45.3±5.3)μg/L vs.(56.3±4.4)μg/L]and in cerebrospinal fluid[(39.2±3.3)μg/L vs.(47.1±3.9)μg/L]were lower in the Donepezil group than in the control group(all P<0.05). Conclusions:Donepezil treatment can downregulate the HMGB1 expression levels in serum and cerebrospinal fluid in Alzheimer's disease patients, which may related to the improvement of cognitive function in Alzheimer's disease patients.
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Objective:To investigate differentially expressed long noncoding RNAs (lncRNAs) and mRNAs between proliferating and involuting infantile hemangioma (IH) .Methods:Eight IH specimens were surgically resected from 4 children with proliferating IH and 4 with involuting IH in Department of Pediatric Surgery, West China Hospital, Sichuan University from January to March in 2019. Differentially expressed lncRNAs and mRNAs between proliferating and involuting IH (a P value < 0.05 and a fold change ≥ 2.0) were screened by microarray analysis, and verified by real-time fluorescence-based quantitative PCR (qRT-PCR) . Bioinformatics analysis was further performed, including GO and KEGG pathway analyses of differentially expressed mRNAs, construction of a lncRNA-mRNA co-expression network, and prediction of cis-acting target genes of differentially expressed lncRNAs. Results:A total of 405 differentially expressed lncRNAs and 772 differentially expressed mRNAs were identified between the proliferating and involuting IH specimens by using microarray technology. Of them, 108 lncRNAs and 107 mRNAs were downregulated, 297 lncRNAs and 665 mRNAs were upregulated in the proliferating IH specimens. Four lncRNAs (n335248, ENST00000450864, n333319, and n335185) and 4 mRNAs (EDNRA, IFI6, HK2, and ITGA1) were verified by qRT-PCR, and the results were consistent with those of microarray analysis. GO and KEGG enrichment analyses showed that differentially expressed mRNAs were mainly involved in the biological processes blood coagulation, axon guidance, angiogenesis and cell adhesion. Besides, differentially expressed mRNAs were mostly enriched in the metabolic pathways focal cell adhesion, regulation of actin cytoskeleton, leukocyte transendothelial migration and phosphatidylinositol 3-kinase/serine-threonine protein kinase and other signaling pathways. In addition, a lncRNA-mRNA co-expression network was constructed with 23 mRNAs and 58 lncRNAs with the degree ≥ 15.Conclusion:Lots of differentially expressed lncRNAs and mRNAs were identified between proliferating and involuting IH tissues, and these lncRNAs may play important roles in the development of IH by regulating corresponding target mRNAs.
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Objective:To preliminarily assess the clinical value of sirolimus combined with prednisone in the treatment of Kaposiform hemangioendothelioma (KHE) complicated by Kasabach-Merritt phenomenon (KMP) .Methods:A retrospective study was conducted. General clinical data and relevant data on efficacy and adverse reactions were collected from 36 patients with KHE complicated by KMP, who received oral sirolimus combined with prednisone in Department of Pediatric Surgery, West China Hospital, Sichuan University from January 2011 to January 2018.Results:Among the 36 patients with KHE complicated by KMP, the male-to-female ratio was 1∶0.8; their average age was 15.0 months (range, 4.0 - 60.0 months) , and the average age of onset was 6.3 months (range, 0.8 - 48.0 months) ; 32 (88.9%) patients were diagnosed with mixed KHE, and 4 (11.1%) with deep KHE; the tumor size ranged from 2.5 cm × 4.0 cm to 20.0 cm × 24.0 cm. During the combined treatment, the average duration of prednisone administration was 6.4 weeks (range, 5.0 - 9.0 weeks) , and that of sirolimus administration was 19.3 months (range, 13.0 - 27.0 months) . After 1-5 weeks of combined treatment, platelet counts and fibrinogen levels of the 36 patients gradually returned to normal. After short-term prednisone combined with long-term sirolimus treatment, the average disease severity score decreased from 4.0 before treatment to 2.4 at 6 months and 1.6 at 12 months. After 12 months of the combined treatment, tumors mostly regressed in 32 (88.9%) patients, partially regressed in 3 (8.3%) , showed no obvious change in 1 (2.8%) . During the treatment, common adverse reactions included gastrointestinal discomfort and oral ulcers, no patient discontinued the treatment due to severe adverse reactions, and no drug toxicity-related death occurred.Conclusion:Sirolimus combined with prednisone is effective and safe for the treatment of KHE complicated by KMP.
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Almost all life on Earth has a 24 h circadian rhythm. The circadian clock that controls the circadian rhythm is an important regulator of physiology and disease. Disturbance of circadian rhythm can negatively affect physiological homeostasis at the molecular, cellular, organ system, and whole organism levels. The circadian clock rhythm disorders are considered to be involved inmany cardiocerebrovascular diseases, such as ischemic stroke and myocardial infarction. Ischemic stroke is one of the main causes of long-term disability and death worldwide. The incidence is higher in the daytime and lower at night, but the exact mechanism of this time distribution is unclear. This article discusses the role of the circadian clock in stroke pathophysiological mechanism and the specific molecular mechanism of clock gene regulation. It is expected that molecular time can be used or changed to open up new targets for stroke treatment.
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Objective@#To investigate the clinical symptoms, treatment intervention and prognosis of Kaposiform lymphangiomatosis(KLA).@*Methods@#Medical information and clinical characteristics data of 8 KLA patients who were admitted to Department of Pediatric Surgery of West China Hospital of Sichuan University from January 2016 to February 2019 were retrospectively reviewed and analyzed. There were 5 males and 3 females with age of 5.8 years old (from 8 months to 29 years old).@*Results@#The lesions in all patients were diffusely distributed. In all 8 patients, the lung and mediastinum were involved with different degrees. Three cases had lesions involving pelvic and abdominal organs. Three cases had lesions involving bones. One case simultaneously involved pelvic and abdominal organs, and 1 case was involved laryngeal and neck. The clinical characteristics were mainly respiratory symptoms. In the laboratory tests, 6 patients had different degrees of thrombocytopenia (minimum 3 × 109/L), and 4 patients had severe fibrinogen reduction (minimum 0.42 g/L). Three patients had prolonged activated partial thromboplastin time (up to 64.2 seconds) and 3 patients had prolonged prothrombin time (up to 18.6 seconds). After surgery (including thoracotomy, chest tube, pericardiocentesis, splenectomy) and empiric medicine therapy (vincristine, sirolimus and corticosteroid), the symptoms improved in 1 case, 2 cases died of complications, 2 cases were stable and 3 cases progressed up to February 2019.@*Conclusions@#KLA is a rare disease that should be differentiated from other types of vascular diseases. Currently, there is no consensus treatment guidelines exist. Accurate diagnosis in KLA can be a challenge. The situation in patients with KLA is prone to rapid deterioration and progress. Future research efforts should seek to develop target-specific drugs for KLA.
ABSTRACT
Claudin proteins are the most crucial components of tight junctions, and play an essential role in maintaining cell polarity, regulating cell permeability and the intercellular ion. In recent years, many studies have shown that abnormality of claudins expression is implicated in the tumor progression. The expression correlates with tumor prognosis and can serve as a biomarker of prognosis and potential therapeutic targets. This review summarizes the current knowledge regarding claudin dysregulation in cancer and highlights the progress in claudin-based treatments.